Mu Fei, Duan Jialin, Bian Haixu, Zhai Xiaohu, Shang Peijin, Lin Rui, Zhao Meina, Hu Dongmei, Yin Ying, Wen Aidong, Xi Miaomiao
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University , Xi'an, China .
Rejuvenation Res. 2017 Aug;20(4):263-277. doi: 10.1089/rej.2016.1884. Epub 2017 Mar 7.
Extract of Salvia miltiorrhiza and Dalbergia Odorifera (SM-DOO) has been traditionally used for the prevention and treatment of cardiovascular diseases. However, information regarding the pharmacodyamic material basis and potential mechanism remain unknown. Male Sprague-Dawley rats were divided into four groups: Sham, Model, Diltiazem, and SM-DOO group, n = 6. Rats were pretreated with homologous drugs for 7 days, and then subjected to 30 minutes of ischemia followed by 180 minutes of reperfusion. Cardioprotection effects of SM-DOO on myocardial ischemia/reperfusion (MI/R) injury rats were examined by hemodynamics, infarct area, histopathology, biochemical indicators, and Western blot analysis. Metabonomics technology was further performed to evaluate the endogenous metabolites profiling systematically. According to the results of pattern recognition analysis, a clear separation of MI/R injury in the Model group and Sham group was achieved and SM-DOO pretreatment group was located much closer to the Sham group than the Model group, which was consistent with results of biochemistry and histopathological assay. Moreover, potential biomarkers were identified to elucidate the drug mechanism of SM-DOO, which may be related with pathways of energy metabolism, especially tricarboxylic acid (TCA) cycle (citric acid) and β-oxidation of fatty acids (3-hydroxybutyric, palmitoleic acid, heptadecanoic acid, and arachidonic acid). In addition, the protein expressions of p-AMPK and p-ACC in the SM-DOO group were significantly elevated, while the levels of carnitine palmitoyl-CoA transferase-1 (CPT-1), p-PDK, and p-PDC were dramatically reduced by SM-DOO. In conclusion, SM-DOO pretreatment could ameliorate MI/R injury by intervening with energy metabolism, especially TCA cycle and β-oxidation of fatty acids. This work showed that the metabonomics method combinate with conventional pharmacological methods is a promising tool in the efficacy and mechanism research of traditional Chinese medicines.
丹参和降香提取物（SM-DOO）传统上用于预防和治疗心血管疾病。然而，关于其药效物质基础和潜在机制的信息仍然未知。将雄性Sprague-Dawley大鼠分为四组：假手术组、模型组、地尔硫䓬组和SM-DOO组，每组n = 6。大鼠用相应药物预处理7天，然后进行30分钟的缺血，随后再灌注180分钟。通过血流动力学、梗死面积、组织病理学、生化指标和蛋白质印迹分析，研究SM-DOO对心肌缺血/再灌注（MI/R）损伤大鼠的心脏保护作用。进一步采用代谢组学技术系统评估内源性代谢物谱。根据模式识别分析结果，模型组和假手术组的MI/R损伤有明显区分，SM-DOO预处理组比模型组更接近假手术组，这与生化和组织病理学检测结果一致。此外，还鉴定出潜在的生物标志物以阐明SM-DOO的药物作用机制，其可能与能量代谢途径有关，尤其是三羧酸（TCA）循环（柠檬酸）和脂肪酸β氧化（3-羟基丁酸、棕榈油酸、十七烷酸和花生四烯酸）。此外，SM-DOO组中p-AMPK和p-ACC的蛋白表达显著升高，而肉碱棕榈酰辅酶A转移酶-1（CPT-1）、p-PDK和p-PDC的水平则显著降低。总之，SM-DOO预处理可通过干预能量代谢，尤其是TCA循环和脂肪酸β氧化来改善MI/R损伤。这项工作表明代谢组学方法与传统药理学方法相结合是研究中药疗效和作用机制的一种有前途的工具。
